We propose the development and use of general and robust late-stage fluorination chemistry for the synthesis of positron emission tomography (PET) tracers for molecular imaging. The innovation of this application relies on conceptually-novel and recently-developed late-stage fluorination chemistry. Here we propose to develop this novel chemical technology further and use it for the synthesis of the PET tracers [18F]-F-DOPA, as a prototype application to improve currently low radiosynthesis yields, and [18F]-PF-02341066, a recently developed anti-neoplastic agent, which has not been amenable to radiolabeling through standard radiosynthetic methods. The labeling of PF-02341066 will allow an increased understanding of the pharmacokinetics and biodistribution of the agent under various conditions, to improve future dosing and timing of administration in patients undergoing therapy for lung cancer. The new advancement in basic science will have a transformative impact on medical imaging by providing conceptually new, rapid, and general approach to the synthesis of currently unavailable PET tracers. We believe that a key strength of this proposal is the assembly of a consortium of four PIs that unifies expert knowledge in chemistry, radiochemistry, imaging probe development, and molecular imaging. Early collaboration that acknowledges the interdependence between chemistry, molecular PET imaging, and preclinical applications is expected to direct the development of innovative chemistry toward its immediate use in applications for PET imaging, informed by the ultimate need in clinical imaging for human health. PUBLIC HEALTH RELEVANCE: Positron-emission tomography (PET) is a powerful non-invasive imaging technology used in clinical care. The current technical difficulties associated with PET are rooted in its underlying technology, radiotracer synthesis, which requires new general and efficient chemical methods.